拉米夫定的疗程及早期应答与疗效的关系

Optimal lamivudine treatment duration and the relationship between its early response and long term effect

目的探讨拉米夫定治疗慢性乙型肝炎的方法与疗效的关系。方法收集179例接受拉米夫定治疗的乙型肝炎e抗原(HBeAg)阳性的慢性乙型肝炎患者的资料,分析早期应答、病毒变异、疗程等与疗效的关系。结果随着治疗时间延长,丙氨酸氨基转移酶(ALT)、HBV DNA、HBeAE和HBeAg/抗-HBe各项指标逐渐改善；1年疗程的HBV DNA阴转率(57．0%)、HBeAg阴转率(39．7%)及HBeAg/抗-HBe转换率(16．8%)均明显高于治疗3个月时的水平(x^2值分别为28．489、33．238、12．690,P＜0．01)。治疗12周时血清HBV DNA水平越低,到治疗52周及随访6个月末时HBV DNA转阴率及HBeAg/抗-HBe血清学转换率越高。疗程为1年、1．5年时,出现HBeAg/抗-HBe转换者HBV DNA反弹率均为40．0%,远低于无转换者(88．2%、85．0%,x^2值分别为12．424、10．237,P＜0．01)。结论拉米夫定治疗是安全有效的,疗程以1．5年为佳。早期应答者疗效较好,如不能在治疗的前3个月内达到DNA应答、1年内出现血清学转换,预示疗效欠佳。

Objective To investigate the relationship between the method of administration of lamivudine and the therapeutic effect of the treatment in patients with chronic hepatitis B virus （HBV） infection. Methods One hundred and seventy-nine patients were given lamivudine 100 mg daily for 1-3 years. The relationships of the therapeutic effect and the early response, YMDD mutants and duration of treatment were analyzed. Results Alanine aminotranferase normalization rate, the negativity rate of HBV DNA and HBeAg, and HBeAg sero-conversion all were increased gradually with prolonged treatment. At the end of l year, HBV DNA negativity rate （57.0%） reached its peak, HBeAg negativity rate （39.7%） and HBeAg sero-conversion rate （16,8%） were higher than those at the end of 3 months （ x^2 = 28.489, 33.238, 12.690, P 〈 0.01）. The lower the HBV DNA level was at the end of 3 months, the higher the HBV DNA negativity and HBeAg sero-conversion rates were at the end of 52 weeks and at the end of the 6 months follow-up. When the duration of treatment reached 1 year and 1.5 years, HBV DNA rebound rate in the patients （40.0% and 40.0% respectively） with HBeAg sero-conversion was obviously less （ x^2 = 12.424, 10.237, P 〈 0.01） than in those without sero-conversion （88.2% and 85.0% respectively）. Conclusion Lamivudine therapy for HBV infection is safe and effective. The optimal duration of treatment was 1.5 years. The early responders had better therapeutic effects. HBV DNA positivity persisting at the end of 3 months medication or no HBeAg sero-conversion in 1 year predicts poor therapeutic effects.